Epidermal growth factor-dependent association of phosphatidylinositol 3-kinase with the erbB3 gene product.
Epidermal growth factor-dependent association of phosphatidylinositol 3-kinase with the erbB3 gene product.
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发表时间：
1994-10
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通讯作者：
Hong-Hee Kim;S. Sierke;J. Koland
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作者：
Hong-Hee Kim;S. Sierke;J. Koland
ErbB 3蛋白是受体蛋白酪氨酸激酶ErbB亚家族的成员。在本研究中，ErbB 3蛋白被磷酸化的机制和这种磷酸化蛋白的信号转导功能进行了研究。当在体外被表皮生长因子受体磷酸化时，ErbB 3蛋白与调节性p85亚基和磷脂酰肌醇（PI）3-激酶的催化活性密切相关。PI 3-激酶与ErbB 3在人乳腺癌细胞中的关联被发现与ErbB 3在酪氨酸残基上的组成性磷酸化相关。在MDA-MB-468乳腺癌细胞中，其中ErbB 3蛋白不是组成性磷酸化的，表皮生长因子的刺激导致ErbB 3酪氨酸残基的磷酸化和涉及ErbB 3蛋白和PI 3-激酶的功能性信号转导复合物的形成。这些结果表明，ErbB 3蛋白可以通过交叉磷酸化机制在酪氨酸残基上磷酸化，并且磷酸化的ErbB 3蛋白可以以类似于胰岛素受体底物1蛋白的方式将其他生长因子受体蛋白酪氨酸激酶偶联至PI 3-激酶途径。
The ErbB3 protein is a member of the ErbB subfamily of receptor protein tyrosine kinases. In the present study, the mechanism by which the ErbB3 protein is phosphorylated and the signal-transducing functions of this phosphorylated protein were investigated. When phosphorylated by the epidermal growth factor receptor in vitro, the ErbB3 protein strongly associated with the regulatory p85 subunit and the catalytic activity of phosphatidylinositol (PI) 3-kinase. The association of PI 3-kinase with ErbB3 in human breast cancer cells was found to be correlated with the constitutive phosphorylation of ErbB3 on tyrosine residues. In MDA-MB-468 breast cancer cells in which the ErbB3 protein is not constitutively phosphorylated, stimulation with epidermal growth factor led to the phosphorylation of ErbB3 on tyrosine residues and the formation of a functional signal transduction complex involving the ErbB3 protein and PI 3-kinase. These results suggest that the ErbB3 protein can be phosphorylated on tyrosine residues by a cross-phosphorylation mechanism and that the phosphorylated ErbB3 protein can couple other growth factor receptor protein tyrosine kinases to the PI 3-kinase pathway in a manner similar to the insulin receptor substrate 1 protein.